Due to overlapping modes of transmission, roughly 30% of human immunodeficiency virus (HIV) infected individuals are co-infected with hepatitis C virus (HCV). While in recent years HIV related morbidity and mortality has been reduced with use of highly active antiretroviral therapy (HAART), HCV infection remains a cause of increased morbidity and mortality in HCV-HIV co-infected individuals as HIV has become a chronic condition. Though liver failure itself may account for a portion of this, HCV co-infection and liver disease are also associated with lower response to hepatitis B virus (HBV) vaccine, and greater cardiovascular disease, significant drivers of poor outcome during HIV infection.
Cardiovascular diseases have become of particular concern due to antiviral-drug-induced metabolic changes, the high prevalence of cardiovascular risk factors in HIV-infected individuals, and growing evidence on HIV-accelerated inflammatory processes that may promote atherosclerosis. In addition, HCV co-infection is associated with a higher prevalence of cardiovascular disease than HIV monoinfection. For example, HCV co-infection is associated with increased risk of cerebrovascular disease and a trend toward increased risk of acute myocardial infarction among HIV-infected patients.
Plasma proteins play a critical role in mediating inflammation and inate immunity. Circulating levels of complement, defense collagens, and cytokines are essential in the immune response, playing roles such as modulation of antigen presentation and T/B-cell maturation/differentiation. Moreover, soluble innate immune molecules have emerged as important molecules in HIV and HCV pathogenesis. However, there remains a need to determine the functional significance of potential biomarkers of disease in the context of immune activation associated with disease progression in chronic viral infections.